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Marked therapeutic efficacy of a novel polyethylene glycol-SN38 conjugate, EZN-2208, in xenograft models of B-cell non-Hodgkin's lymphoma.
- Source :
-
Haematologica [Haematologica] 2009 Oct; Vol. 94 (10), pp. 1456-9. - Publication Year :
- 2009
-
Abstract
- Examination of the clinical utility of SN38 (10-hydroxy-7-ethyl-camptothecin), the active metabolite of CPT-11, has not been possible to date due to poor solubility of SN38. Here we evaluated the activity of EZN-2208, a water-soluble polyethyleneglycol-SN38 conjugate, in pre-clinical models of Burkitt's non-Hodgkin's lymphoma (NHL) (Raji and Daudi), and follicular NHL (DoHH2). In vitro, the IC50 of EZN-2208 ranged from 3-24 nM, which was 30- to 45-fold lower than CPT-11 or 2.5- to 3.5-fold higher than SN38. In both an early-disease Raji model and an advanced-disease Daudi model, treatment with multiple doses of EZN-2208 resulted in 90% and 100% cures of animals, respectively (cure defined as no sign of tumors by gross observations at the termination of study). The activity of EZN-2208 was dramatically superior to that of CPT-11 in all three models. The excellent therapeutic efficacy of EZN-2208 in several B-cell NHL xenograft models merits its evaluation in the clinic for lymphoid malignancies.
- Subjects :
- Animals
Burkitt Lymphoma drug therapy
Burkitt Lymphoma pathology
Camptothecin chemistry
Camptothecin therapeutic use
Cell Line, Tumor
Female
Humans
Lymphoma, B-Cell pathology
Mice
Mice, SCID
Camptothecin analogs & derivatives
Lymphoma, B-Cell drug therapy
Polyethylene Glycols chemistry
Polyethylene Glycols therapeutic use
Xenograft Model Antitumor Assays methods
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 94
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 19794091
- Full Text :
- https://doi.org/10.3324/haematol.2009.008276